EP0718038A2 - Appareil pour la séparation de mélanges de particules diélectriques de taille microscopique suspendues dans un fluide ou un gel - Google Patents

Appareil pour la séparation de mélanges de particules diélectriques de taille microscopique suspendues dans un fluide ou un gel Download PDF

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Publication number
EP0718038A2
EP0718038A2 EP96103459A EP96103459A EP0718038A2 EP 0718038 A2 EP0718038 A2 EP 0718038A2 EP 96103459 A EP96103459 A EP 96103459A EP 96103459 A EP96103459 A EP 96103459A EP 0718038 A2 EP0718038 A2 EP 0718038A2
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EP
European Patent Office
Prior art keywords
electrodes
particles
film
particle
electrode
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP96103459A
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German (de)
English (en)
Other versions
EP0718038B1 (fr
EP0718038A3 (fr
Inventor
Wolfgang Benecke
Bernd Wagner
Rolf Hagedorn
Günter FUHR
Torsten Müller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Original Assignee
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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Publication of EP0718038A2 publication Critical patent/EP0718038A2/fr
Publication of EP0718038A3 publication Critical patent/EP0718038A3/fr
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Publication of EP0718038B1 publication Critical patent/EP0718038B1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B03C5/028—Non-uniform field separators using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/005—Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B03C5/026—Non-uniform field separators using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/0005—Field flow fractionation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00819—Materials of construction
    • B01J2219/00824—Ceramic
    • B01J2219/00828—Silicon wafers or plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00851—Additional features
    • B01J2219/00853—Employing electrode arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00905—Separation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00925—Irradiation
    • B01J2219/0093—Electric or magnetic energy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/0005—Field flow fractionation
    • G01N2030/0015—Field flow fractionation characterised by driving force
    • G01N2030/0035—Field flow fractionation characterised by driving force electrical field

Definitions

  • the invention relates to a device for separating mixtures of microscopic dielectric particles, in which the particle mixture is suspended in a liquid or a gel.
  • Separation devices of this type are intended to isolate mixtures of microscopic particles, such as biological cells, cell organelles, biomolecules and inorganic, dielectric particles, and to prepare them for investigations or technical applications.
  • the separation of certain types of particles from particle mixtures is required, for example, in medicine, food technology, biology, chemistry and pharmacy. Especially when larger amounts of a mixture are to be separated, it is desirable to use a continuous separation process.
  • the convection is reduced either by cooling or by using convection-preventing carriers.
  • convection-preventing carriers There are limits when it comes to separating relatively large particles, such as biological cells, or when working in continuous operation. Continuous operation can therefore only be achieved by complex cooling techniques or by complicated stabilization techniques, for example by using centrifugal forces.
  • WO-92/97657 discloses a method for handling microscopic, dielectric particles and a device for carrying out the method, which is essentially limited to electrode arrangements with which a straight, concentrated particle guidance within an alternating electric field is possible. With the electrode arrangements described therein, microscopic, dielectric particles can be guided through narrow channels on straight lines in order to position them in a contact-free manner for examinations at different target locations.
  • Electrode devices are known, with the aid of which microbiological particles, preferably cells, are deflected from a preferred direction, which is predetermined by the flow of a carrier liquid.
  • microbiological particles preferably cells
  • certain cell reactions are stimulated and supported by bringing certain particles into spatial contact.
  • the electrode structures must be selected accordingly, so that particle accumulations are possible in certain areas.
  • FIGS. 7 a and b show the use of two independently controlled electrode pairs, as shown in FIGS. 7 a and b. Both pairs of electrodes are operated in such a way that certain particle particles can accumulate on their electrode surfaces. If the surfaces are completely covered with the particles, the separation process must be interrupted. Furthermore, the arrangement of a flowing fluid in which the particles to be investigated.
  • the invention has for its object to provide a device for separating mixtures of microscopically small, suspended particles, which operates continuously, has a high separation quality and can be implemented inexpensively.
  • the device should be able to largely avoid the troublesome convection phenomena within the particle mixtures to be separated, without great expenditure on equipment.
  • the suspended particles are forced onto guideways by the flow of a suspension medium.
  • an additional force compensates for the forces which force the particles onto the guideways, so that they are decoupled from the guideways and thus separated from the mixture.
  • the additional force field is due to a high frequency Alternating field provided.
  • the electrodes have openings or pores through which the particles can be removed. In this way, continuous operation is possible.
  • the decoupling of certain types of particles can be adjusted by varying the additional force field or by varying the force acting on the particles through the flowing suspension medium, depending on the desired selection.
  • the device thus provides a so-called guiding field, suspension medium flowing in a predeterminable direction, which forces the particles to be separated on guideways.
  • a dielectrophoretic high-frequency field acts on the particles, which, while compensating for the force acting on the particles due to the flow, decouples them from the flow.
  • Electrode systems are arranged along the guide channel, with the aid of which inhomogeneous electrical alternating fields are generated in the flow channel. Due to the field inhomogeneities, dielectrophoretic forces act on the particles, which, depending on the flow velocity and field strength, couple certain types of particles out of the mixture.
  • the inhomogeneous fields by means generated two electrodes arranged in parallel, which enclose the flow channel, and whose mutually facing surfaces have relief-like surface irregularities such as peaks and valleys.
  • the selection of the decoupled particle type is based on the frequency or strength of the high-frequency AC voltage applied between the plates.
  • the inhomogeneous fields are generated with the aid of two rows of electrodes arranged parallel to one another, which enclose the flow channel.
  • the field inhomogeneities are achieved in that the electrodes of one row are spaced differently and alternating voltages are applied between adjacent electrodes of a row which differ in strength and frequency from the voltages applied between adjacent electrodes of the other row.
  • a further embodiment of such a device is characterized in claim S.
  • An elongated film, on the two sides of which electrodes rows perpendicular to one another are applied, is closed rolled up in a roll.
  • Insulating webs, which are applied to the electrodes on one side of the film in the direction of the roll axis, serve as spacers between the coiled layers, so that the suspension can flow through the roll along its figure axis.
  • the desired particle type is extracted from the mixture by suitably applying a high-frequency AC voltage to the rows of electrodes on both sides.
  • the elements delimiting the particle path have passable openings or are made of porous material.
  • the outcoupled particles can escape from the flow channel through the openings.
  • Such openings can be achieved particularly easily by using an ultra-thin membrane as the main body of the device, into which openings are etched.
  • the electrode surfaces have relief-like structures, preferably longitudinal channels in the direction of the flow of the suspension medium. This avoids lateral deflection of the uncoupled, flowing particles and calms the flow. By calming the flow, the separation quality is increased.
  • a further development of the invention according to claim 8 serves to influence the running properties of the flowing particles.
  • the insulation layer on the electrodes which has locally different thicknesses, leaves the electric field different at different points act strongly on the particles. In this way, the particle flow can be manipulated effectively, since different preferred tracks for the particles can be created at different points in the device.
  • the trough-shaped and undulating structure of the coating serves to calm and flexibly guide the particle flow.
  • a device according to the invention preferably consists of materials which are used in microstructure technology and microelectronics and is produced using the methods customary there.
  • the base body to which the electrodes are applied preferably consists of silicon, the electrodes of gold.
  • the separation device is integrated together with an electronic circuit for controlling the electrodes and for evaluating the particle movement on a common base body, preferably a silicon wafer.
  • the device according to the invention is well suited for cascading.
  • the quality of separation is significantly increased by connecting several separating devices in series. Good results can be achieved if a decoupled partial stream is fed back to the output device and the cascade is run through again. In many cases, a very high separation quality is achieved when a decoupled partial stream is fed back by one or two separation stages.
  • the advantages achieved with the invention are in particular in that the proposed separation of the mixture has a threshold value character in contrast to conventional separation processes.
  • the separation therefore only depends on whether a certain type of particle can leave its management or not.
  • the threshold value determining the separation can be chosen flexibly due to the easily influenceable relationship between the dielectric managers and the deflecting force components. This makes it easy to determine the type of particle to be coupled out and at the same time a high separation quality is achieved.
  • the electrodes 31 and 32 enclose a flow channel 33.
  • the incoming particle stream is indicated by an arrow.
  • the mixture of particles is moved by the flow of the suspension medium through the device. Dielectrophoretic forces couple particles of a certain type out of the mixture in channel 33.
  • the field inhomogeneities required for this are generated by the surface irregularities of the electrodes 31, 32.
  • the type of particles to be coupled out is selected by the choice of the frequency and strength of the high-frequency alternating voltage U (f) applied between the electrodes 31, 32.
  • the surfaces of the electrodes 31, 32 are structured by etching processes.
  • FIG. 2 shows an electrode arrangement for coupling out particles from the stream of a suspended particle mixture.
  • Two rows of electrodes 41, 42 enclose a flow channel 43 through which the suspended particle mixture represented by an arrow flows.
  • the elongated electrodes 41, 42 of the two rows are arranged parallel to one another, unequally spaced apart. Adjacent electrodes in a row are connected to different poles of a high-frequency voltage source.
  • the particles to be coupled out are selected by setting the applied field frequencies f1, f2 or via the selected voltages U1, U2.
  • Electrode systems 52, 53 are applied on both sides to an elongated film 51. Both the electrodes 52 running parallel to the longitudinal direction of the film on one film surface and the electrodes 53 running perpendicular to the longitudinal direction of the film on the other film surface are conductively connected to one another at one end. Insulating bridges 54 are attached at regular intervals above the electrodes 52 and, after the film has been rolled up, prevent electrical contact between the electrode systems and keep flow-through spaces open for the flow of the suspended particle mixture. The flow of the particle mixture through the roller is indicated by arrows. Dielectrophoretic holding fields are used to couple out certain types of particles from the flowing mixture of particles. The holding fields are generated by applying a high-frequency AC voltage between the electrode systems.
  • FIG. 4 shows a cascade-shaped separation section.
  • Five separation devices (as shown, for example, in FIG. 2) are arranged one behind the other.
  • the arrows 4 indicate that in this area, by combining the dielectrophoresis and an additional force, the particle mixture 1 is broken down into two fractions 2, 3.
  • the fraction from the mixture decoupled particle type 2 passes through further separation stages for cleaning remaining particles of the mixture, in order to obtain the particles of type 2 remaining in fraction 3, particle fraction 3 is moved to the beginning of the cascade, for example, by an electrical, high-frequency traveling field 5 or one at a time Separation stage returned.
  • a particularly high separation quality is achieved with the help of the cascade-shaped separation section.
EP96103459A 1991-08-19 1992-08-19 Appareil pour la séparation de mélanges de particules diélectriques de taille microscopique suspendues dans un fluide ou un gel Expired - Lifetime EP0718038B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4127405 1991-08-19
DE4127405A DE4127405C2 (de) 1991-08-19 1991-08-19 Verfahren zur Trennung von Gemischen mikroskopisch kleiner, in einer Flüssigkeit oder einem Gel suspendierter dielektrischer Teilchen und Vorrichtung zur Durchführung des Verfahrens
EP92918105A EP0599957B1 (fr) 1991-08-19 1992-08-19 Procede et dispositif de separation en continu de melanges de particules dielectriques microscopiques

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP92918105A Division EP0599957B1 (fr) 1991-08-19 1992-08-19 Procede et dispositif de separation en continu de melanges de particules dielectriques microscopiques
EP92918105.5 Division 1992-08-19

Publications (3)

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EP0718038A2 true EP0718038A2 (fr) 1996-06-26
EP0718038A3 EP0718038A3 (fr) 1996-08-28
EP0718038B1 EP0718038B1 (fr) 2002-10-09

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EP92918105A Expired - Lifetime EP0599957B1 (fr) 1991-08-19 1992-08-19 Procede et dispositif de separation en continu de melanges de particules dielectriques microscopiques
EP96103459A Expired - Lifetime EP0718038B1 (fr) 1991-08-19 1992-08-19 Appareil pour la séparation de mélanges de particules diélectriques de taille microscopique suspendues dans un fluide ou un gel

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EP92918105A Expired - Lifetime EP0599957B1 (fr) 1991-08-19 1992-08-19 Procede et dispositif de separation en continu de melanges de particules dielectriques microscopiques

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US (1) US5454472A (fr)
EP (2) EP0599957B1 (fr)
JP (1) JP3453136B2 (fr)
DE (4) DE4143573C2 (fr)
WO (1) WO1993003850A1 (fr)

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JPH06509745A (ja) 1994-11-02
DE4127405A1 (de) 1993-02-25
DE59209969D1 (de) 2002-11-14
EP0718038B1 (fr) 2002-10-09
EP0599957A1 (fr) 1994-06-08
US5454472A (en) 1995-10-03
DE4127405C2 (de) 1996-02-29
JP3453136B2 (ja) 2003-10-06
WO1993003850A1 (fr) 1993-03-04
EP0718038A3 (fr) 1996-08-28
DE59207522D1 (de) 1996-12-19
DE4143573C2 (de) 1996-07-04
EP0599957B1 (fr) 1996-11-13

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